Recent advances, perhaps most visible in the Human Genome Initiative, have presented new and compelling means and objectives to exploit the exquisite specificity of nucleic acid hybridization. Precise knowledge of the temperature dependent stability of nucleic acid (and nucleic acid analog) complexes is necessary for the rational design and optimization of hybridization probes for use in high throughput screening, nucleic acid based diagnostics and therapeutics, and numerous emerging biotechnology applications. The primary objective of the proposed project is to develop a high-throughput means of obtaining accurate thermal and thermodynamic data for nucleic acid complexes by measurement and analysis of optically-monitored, temperature-induced, order-disorder transitions. The proposed device will operate analogously to a pH meter, the operator will load a nucleic acid complex sample and after a short settling time a numerical result will be displayed. The device will provide, in a matter of seconds, a complete thermodynamic analysis capable of predicting accurately the stability of the nucleic acid complex at any temperature. PUBLIC HEALTH RELEVANCE: The primary objective of the proposed project is to develop a high-throughput means of obtaining accurate thermal and thermodynamic data for nucleic acid complexes by measurement and analysis of optically- monitored, temperature-induced, order-disorder transitions. This information is useful in designing and troubleshooting probes and in more fundamental studies of nucleic acids.